title: The roles of MMP-9/TIMP-1 in cerebral edema following experimental acute cerebral infarction in rats.
abstract: Matrix metalloproteinases 9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1), regulate homeostasis and turnover of the extra cellular matrix (ECM). They play important roles in acute cerebral infarction (ACI). The contributions of MMP-9 and TIMP-1 to the early stages of ACI are not completely understood. This study investigates the time course of MMP-9 and TIMP-1 and their relations to edema after ACI in rats. Serum concentrations of MMP-9 and TIMP-1 protein were measured using ELISA and mRNA level were measured using real-time PCR. Brain samples were harvested and the brain water content (BWC) was measured. Results revealed that MMP-9 concentration increased fast during the first 12 h after ACI, while after 12 h the increase was much slower. The MMP-9 protein concentration was elevated earlier than the mRNA level. BWC increased starting at 6 h after ACI to reach a peak at 12 h and decreased back to normal levels at 72 h. Both the MMP-9 protein and its mRNA were positively correlated with BWC, however no correlation was found between TIMP-1 levels and BWC. The MMP-9/TIMP-1 protein ratio was more closely correlated with BWC than the MMP-9 concentration. These results indicate that brain edema induced by ACI is associated with increased MMP-9 levels and MMP-9/TIMP-1 ratio in serum.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Dan-Dong
authors.initials: DD
authors.lastname: Li
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Song
authors.forename: Huan
authors.initials: H
authors.lastname: Huang
authors.forename: Xiao-Ye
authors.initials: XY
authors.lastname: Guo
authors.forename: Ji-Yang
authors.initials: JY
authors.lastname: An
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Pang
authors.forename: Yong-Lin
authors.initials: YL
authors.lastname: Zhao
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D020520:Brain Infarction / Q000097:blood / Q000150:complications / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism*; D051381:Rats; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000378:metabolism*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9
keywords: ACI; Acute cerebral infarction; BBB; MCAO; MMP; MMP-9/TIMP-1; Matrix metalloproteinase-9; Rat; TIMP; Tissue inhibitors of metalloproteinases-1; acute cerebral infarction; blood–brain barrier; matrix metalloproteinase; middle cerebral artery occlusion; tissue inhibitor of metalloproteinase